Behavioral effects in animals and psychotomimetic action in humans of certain (+) alkyl-N-normetazocines as well as movement disorder side effects of certain antipsychotic drugs may be mediated by sigma receptors. The goal of the present application is to generate a graphical model consistent with present receptor binding data on the sigma receptor and then to suggest on the basis of the model new experiments that will provide a better understanding of the receptor topography. The specific is to determine the structural features of (+)-N- alkylbenzomorphans required for potent selective binding to the sigma receptor. This will involve the design, synthesis, receptor binding, and in vivo evaluation of (+)-N-alkylbenzomorphans Molecular modeling- molecular mechanics studies were used to design the compounds proposed for study. Pharmacological studies on the synthesized compounds will include: (1) radioligand binding competitive experiments against (+)- [3H]-SKI- 10.047 and [3H]-di-o-tolylguanidine (DTG) in the rat brain, and (2) in vivo studies in rats. The absence of PCP binding will be shown by the inability to inhibit binding of [3H]-TCP in the rat. The development of new, more selective and less toxic sigma ligand binding compounds is of particular interest since this will lead to a better understanding of the neurophysiological relevance of the sigma receptor. In addition to providing new and unique tools for biochemical and pharmacological studies, the information could translate into new antipsychotic agents or sigma receptor antagonists useful in conjunction with present antipsychotic drugs such as haloperidol.